Interleukin 2 (IL-2) has demonstrated a potent ability to augment NK activity and to generate killer cells against NK-insensitive targets and secrete IFN-gamma by LGL. In addition to LGL activity being regulated by a variety of cytokines, LGLs have been shown to produce a variety of lymphokines (IL-1, IFN, CSF, BCGF). A project is being conducted to investigate IFN gene expression and regulation in highly purified human LGLs and T cells. Within 1 hr of IL-2 treatment of freshly isolated human LGLs, IFN-gamma mRNA secreted in the culture medium within 4-6 hr of treatment. These results indicate that with certain stimuli LGLs may be the predominant source of IFN-gamma from peripheral blood lymphocytes. In addition to IL-2, MoAbs to specific surface proteins have been used to study their role of these proteins as potential regulatory elements in the activation of LGLs. The CD3- LGL represents an excellent cell type to study signal transduction leading to both modulations of cytotoxicity and gene transcription, since it represents a cell type "poised" for activation and capable of responding to a single stimulus. Present studies involve examining agents which modulate signal transduction of IL-2 and IFN mediated events.